Brief Summary
The goal of this study is to evaluate changes in body composition among patients who are treated with cyclin-dependent kinase (CDK) 4/6 inhibitors (abemaciclib, ribociclib, or palbociclib).
Brief Title
CDK and Body Composition Study
Detailed Description
The goal of this study is to evaluate changes in body composition among patients who are treated with cyclin-dependent kinase (CDK) 4/6 inhibitors (abemaciclib, ribociclib, or palbociclib). There is preliminary data suggesting that these drugs have more effect on body fat mass than body muscle mass. These drugs have already been approved by U.S Food and Drug Administration (FDA) to treat ER+/HER2- metastatic breast cancer. The investigators will follow up body composition changes among patients who receive CDK 4/6 inhibitors as part of their standard of care. Body composition changes will be measured from CT or PET/CT scans that are part of standard of care treatment, and from DEXA scans (DEXA will be performed only if available). The investigators will also conduct body measurements with measuring tape and will draw blood tests to assess for fat biomarkers.
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Phone
718-405-8505
Central Contact Email
janampa@montefiore.org
Central Contact Role
Contact
Central Contact Phone
718-405-8126
Central Contact Email
eshernande@montefiore.org
Completion Date
Completion Date Type
Estimated
Conditions
Breast Cancer
Eligibility Criteria
Inclusion Criteria:
* Histologically confirmed adenocarcinoma of the breast that is ER and/or PR positive based on current ASCO-CAP guidelines
* Metastatic or locally advanced/inflammatory, unresectable breast cancer not amenable to potentially curative surgery
* Measurable and/or non-measurable as defined by RECIST 1.1 criteria
* Patients must be a candidate to start an FDA approved CDK 4/6 inhibitor (palbociclib, ribociclib, abemaciclib) as part of standard of care treatment
* Female, or male patients, and age \>=18 years
* ECOG performance status 0-2
* Ability to understand and the willingness to sign a written informed consent document
* Concomitant therapy with bisphosphonates, RANKL inhibitors or growth-colony-stimulating factor (G-CSF) is allowed as per physician decision
Exclusion Criteria:
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to CDK 4/6 inhibitors or other agents used in the study (e.g., fulvestrant, letrozole, anastrozole, exemestane)
* BMI \< 18.5
* Prior CDK 4/6 use in any setting
* Inability to undergo anthropometric measurements
* Inability to undergo CT scan imaging
* Women of child-bearing potential must not be pregnant or breast feeding. They must also agree to use adequate contraception (hormonal or barrier method of birth control) and not be breast feeding prior to study entry, for the duration of study participation, and for up to 10 days after completion of all protocol therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study or up to 10 days after completion of protocol therapy, she should inform her treating physician immediately
* Intercurrent illness that would substantially increase the risk of treatment associated complications (e.g., active infection, uncontrolled diabetes mellitus or hypertension)
* Psychiatric illness/social situations that would interfere with the patient's ability to comply with the treatment regimen
* Patients with untreated brain metastasis are excluded. Patients with a prior history of brain metastasis are eligible if they have received prior brain radiation (whole brain or stereotactic radiosurgery) or surgery, have stable intracranial disease for at least 3 months after completion of local therapy, and are not taking corticosteroids for treatment of brain metastasis
* Patients who have not recovered (i.e., CTCAE Grade ≤1 or baseline) from an adverse event due to a previously administered agent, excluding alopecia
* Patients with inability to swallow and retain pills
* Malabsorption syndrome or other gastrointestinal illness that could affect oral absorption
* Patients with active implanted medical devices (cardiac pacemakers, defibrillators or patients connected to electronic life support devices)
* Histologically confirmed adenocarcinoma of the breast that is ER and/or PR positive based on current ASCO-CAP guidelines
* Metastatic or locally advanced/inflammatory, unresectable breast cancer not amenable to potentially curative surgery
* Measurable and/or non-measurable as defined by RECIST 1.1 criteria
* Patients must be a candidate to start an FDA approved CDK 4/6 inhibitor (palbociclib, ribociclib, abemaciclib) as part of standard of care treatment
* Female, or male patients, and age \>=18 years
* ECOG performance status 0-2
* Ability to understand and the willingness to sign a written informed consent document
* Concomitant therapy with bisphosphonates, RANKL inhibitors or growth-colony-stimulating factor (G-CSF) is allowed as per physician decision
Exclusion Criteria:
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to CDK 4/6 inhibitors or other agents used in the study (e.g., fulvestrant, letrozole, anastrozole, exemestane)
* BMI \< 18.5
* Prior CDK 4/6 use in any setting
* Inability to undergo anthropometric measurements
* Inability to undergo CT scan imaging
* Women of child-bearing potential must not be pregnant or breast feeding. They must also agree to use adequate contraception (hormonal or barrier method of birth control) and not be breast feeding prior to study entry, for the duration of study participation, and for up to 10 days after completion of all protocol therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study or up to 10 days after completion of protocol therapy, she should inform her treating physician immediately
* Intercurrent illness that would substantially increase the risk of treatment associated complications (e.g., active infection, uncontrolled diabetes mellitus or hypertension)
* Psychiatric illness/social situations that would interfere with the patient's ability to comply with the treatment regimen
* Patients with untreated brain metastasis are excluded. Patients with a prior history of brain metastasis are eligible if they have received prior brain radiation (whole brain or stereotactic radiosurgery) or surgery, have stable intracranial disease for at least 3 months after completion of local therapy, and are not taking corticosteroids for treatment of brain metastasis
* Patients who have not recovered (i.e., CTCAE Grade ≤1 or baseline) from an adverse event due to a previously administered agent, excluding alopecia
* Patients with inability to swallow and retain pills
* Malabsorption syndrome or other gastrointestinal illness that could affect oral absorption
* Patients with active implanted medical devices (cardiac pacemakers, defibrillators or patients connected to electronic life support devices)
Inclusion Criteria
Inclusion Criteria:
* Histologically confirmed adenocarcinoma of the breast that is ER and/or PR positive based on current ASCO-CAP guidelines
* Metastatic or locally advanced/inflammatory, unresectable breast cancer not amenable to potentially curative surgery
* Measurable and/or non-measurable as defined by RECIST 1.1 criteria
* Patients must be a candidate to start an FDA approved CDK 4/6 inhibitor (palbociclib, ribociclib, abemaciclib) as part of standard of care treatment
* Female, or male patients, and age \>=18 years
* ECOG performance status 0-2
* Ability to understand and the willingness to sign a written informed consent document
* Concomitant therapy with bisphosphonates, RANKL inhibitors or growth-colony-stimulating factor (G-CSF) is allowed as per physician decision
* Histologically confirmed adenocarcinoma of the breast that is ER and/or PR positive based on current ASCO-CAP guidelines
* Metastatic or locally advanced/inflammatory, unresectable breast cancer not amenable to potentially curative surgery
* Measurable and/or non-measurable as defined by RECIST 1.1 criteria
* Patients must be a candidate to start an FDA approved CDK 4/6 inhibitor (palbociclib, ribociclib, abemaciclib) as part of standard of care treatment
* Female, or male patients, and age \>=18 years
* ECOG performance status 0-2
* Ability to understand and the willingness to sign a written informed consent document
* Concomitant therapy with bisphosphonates, RANKL inhibitors or growth-colony-stimulating factor (G-CSF) is allowed as per physician decision
Gender
All
Gender Based
false
Keywords
cyclin-dependent kinase (CDK) 4/6 inhibitors
Body composition
body fat mass
metastatic ER+/HER2- breast cancer
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT03697577
Org Class
Other
Org Full Name
Montefiore Medical Center
Org Study Id
2018-9567
Overall Status
Recruiting
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
Pilot Study Assessing the Effect of Cyclin-dependent Kinase 4/6 Inhibitors on Body Composition in Patients With ER+/HER2- Metastatic Breast Cancer
Primary Outcomes
Outcome Description
Total Adipose tissue (TAT) is defined as the sum of intramuscular adipose tissue (IMAT), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) obtained from L3 cross section from CT scans.
Outcome Measure
Total adipose tissue (TAT)
Outcome Time Frame
Baseline and 6 months after CDK 4/6 inhibitor therapy
Secondary Outcomes
Outcome Description
Body Fat Mass will be obtained from dual-energy x-ray absorptiometry (DEXA). The DEXA scan calculates the ratio of soft tissue attenuation at different X-ray energies. Results are measured and reported in kilograms (kg). DEXA will be performed only if available.
Outcome Time Frame
Baseline and 6 months after CDK 4/6 inhibitor therapy
Outcome Measure
Body Fat Mass (BFM) using Dual-energy X-ray Absorptiometry (DEXA)
Outcome Description
Body Lean Mass (BLM) will be obtained from dual-energy x-ray absorptiometry (DEXA). The DEXA scan calculates the ratio of soft tissue attenuation at different X-ray energies. Results are measured and reported in kilograms (kg). DEXA will be performed only if available.
Outcome Time Frame
Baseline and 6 months after CDK 4/6 inhibitor therapy
Outcome Measure
Body Lean Mass (BLM) using Dual-energy X-ray Absorptiometry (DEXA)
Outcome Description
Skeletal muscle index (SMI) will be obtained by dual-energy x-ray absorptiometry (DEXA). The DEXA scan will be used to measure the amount of lean muscle in the body. SMI is defined as muscle area at L3 cross section from CT scans in cm\^2 divided by height in meters squared. DEXA will be performed only if available.
Outcome Time Frame
Baseline and 6 months after CDK 4/6 inhibitor therapy
Outcome Measure
Skeletal muscle index (SMI)
Outcome Description
Fasting glucose levels in blood sera will be measured using a glucose blood sugar test. Normal ranges vary based on the health of the individual however standard glucose concentrations are between 70 mg/dL (3.9 mmol/L) -100 mg/dL (5.6 mmol/L). Glucose levels between 100-125 mg/dL (5.6-6.9 mmol/L) may be indicative of prediabetes. Fasting glucose levels \>126 mg/dL on successive tests is correlated with diabetes. Results will be summarized and reported.
Outcome Time Frame
Baseline and 3 months and 6 months after CDK 4/6 inhibitor therapy
Outcome Measure
Adipose Serum Biomarkers - Fasting Glucose
Outcome Description
A lipid panel will be used to assess Total cholesterol, LDL Cholesterol, HDL Cholesterol, and triglyceride levels in blood sera samples. Each parameter has unique ranges and can vary by age, weight, and sex; however, High concentrations of Total cholesterol and LDL cholesterol increases the risk of coronary heart disease and atherosclerosis. HDL cholesterol ("good cholesterol") removes excess cholesterol from the body. High triglyceride levels also increase the risk of cardiovascular disease. Results for each parameter will be summarized and reported in mg/dL.
Outcome Time Frame
Baseline and 3 months and 6 months after CDK 4/6 inhibitor therapy
Outcome Measure
Adipose Serum Biomarkers - Lipid Panel (Total Cholesterol and LDL cholesterol, HDL cholesterol, and Triglycerides)
Outcome Description
DHEAS levels in blood sera will be measured using a DHEA-sulfate (DHEAS) blood test. This test can be used to check the function of the adrenal glands. Normal ranges vary based on age, gender and laboratory; however, high concentrations could be indicative of adrenal tumors, Cushing's disease, polycystic ovary syndrome (PCOS), or adrenal hyperplasia. Results will be summarized and reported in ug/dL.
Outcome Time Frame
Baseline and 3 months and 6 months after CDK 4/6 therapy
Outcome Measure
Adipose Serum Biomarkers - Dehydroepiandrosterone Sulphate (DHEAS)
Outcome Description
Insulin levels in blood sera will be measured using an insulin blood test. Insulin is a hormone that regulates glucose absorption. Normal ranges vary based on the type of test administered and the health of the individual; however, standard fasting insulin concentrations are usually \<25 mIU/L. Higher concentrations can be indicative of insulin resistance. Results will be summarized and reported.
Outcome Time Frame
Baseline and 3 months and 6 months after CDK 4/6 inhibitor therapy
Outcome Measure
Adipose Serum Biomarkers - Insulin
Outcome Description
Leptin will be assessed using a leptin blood test that measures the concentration of leptin in blood sera. Leptin is a hormone that helps regulate appetite and energy levels. Standard ranges vary based on age, gender, body mass index, and other variables; however, ranges are generally between 0.5-15.2 ng/mL for females and 0.5-12.5 ng/mL for males. Results will be summarized and reported.
Outcome Time Frame
Baseline and 3 months and 6 months after CDK 4/6 inhibitor therapy
Outcome Measure
Adipose Serum Biomarkers - Leptin
Outcome Description
FLI will be assessed by blood test and calculated as the ratio of total leptin and soluble leptin receptor (sOB-R) concentrations. FLI is a biomarker of leptin resistance and the status of leptin action. High FLI is a risk factor for obesity and is associated with several chronic diseases. Results will be summarized and reported.
Outcome Time Frame
Baseline and 3 months and 6 months after CDK 4/6 inhibitor therapy
Outcome Measure
Adipose Serum Biomarkers - Free Leptin Index (FLI)
Outcome Description
Adiponectin will be assessed using an adiponectin test that measures the concentration of adiponectin in the blood. Adiponectin is a protein hormone produced by fat cells that helps regulate blood sugar and fat metabolism. Lower levels of adiponectin in blood sera are often linked to conditions like obesity, type 2 diabetes, and heart disease. A normal adiponectin blood test result is generally 5-30 ug/mL but can vary depending on age and body mass index (BMI). Results will be summarized and reported.
Outcome Time Frame
Baseline and 3 months and 6 months after CDK 4/6 inhibitor therapy
Outcome Measure
Adipose Serum Biomarkers - Adiponectin
Outcome Description
hsCRP will be measured and reported by blood test. hsCRP measures the concentration of C-reactive protein (CRP) in blood. CRP is a protein that increases in response to inflammation and is correlated with adverse cardiovascular and cerebrovascular outcomes. Normal results are generally risk stratified with concentrations \<1.0 mg/dL indicating a low risk of cardiovascular disease; concentrations between 1.0-3.0 mg/dL indicating an average risk of cardiovascular disease; and concentrations \>3.0 mg/dL indicating a high risk of cardiovascular disease. Results will be summarized and reported.
Outcome Time Frame
Baseline and 3 months and 6 months after CDK 4/6 inhibitor therapy
Outcome Measure
Adipose Serum Biomarkers - High-sensitivity C-reactive protein (hsCRP)
Outcome Description
BFM will be measured with the use of bioimpedance spectroscopy (BIS). BIS is a non-invasive method that takes measurements at 256 different frequencies and uses mathematical modeling to calculate electrical resistance throughout the body. Fat tissue has significantly higher resistance compared to lean muscle tissue. The total weight of body fat estimated by the BIS analysis will be expressed in kilograms and summarized for the group.
Outcome Time Frame
Baseline and 3 months and 6 months after CDK 4/6 inhibitor therapy, and every 3 months thereafter up to 24 months
Outcome Measure
Body Fat Mass (BFM) using Bioimpedance spectroscopy (BIS)
Outcome Description
FFM will be derived based on the BFM readout obtained from the BIS analysis. The "fat-free mass" will be calculated by subtracting the total body weight minus the estimated BFM obtained by BIS analysis, based on electrical resistance through the body. This result will be expressed in kilograms and summarized for the group.
Outcome Time Frame
Baseline and 3 months and 6 months after CDK 4/6 inhibitor therapy, and every 3 months thereafter up to 24 months
Outcome Measure
Body Fat-Free Mass (FFM)
Outcome Description
BMI will be determined by obtaining height and body weight measurements. It is calculated by dividing body weight in kilograms (kg) by height in meters squared (m\^2). A BMI of 30 kg/m\^2 or higher has been used to define obesity in most reports, including those showing an association between obesity and increased risk of cancers, cancer mortality, and mortality from all causes. Group results will be summarized and reported.
Outcome Time Frame
Baseline and every 4 weeks for the first 6 months after CDK 4/6 inhibitor therapy and every 3 months thereafter up to 24 months
Outcome Measure
Anthropometric measurements - Body Mass Index (BMI)
Outcome Description
Skin fold thickness will be measured with the use of calipers. Skin fold thickness measurements will be obtained for the biceps, triceps, subscapular, and suprailiac sites. Calipers will be used to pinch the skin and lift it away from the muscle at each site and measure the thickness of skin folds at each location. Values will be summarized in millimeters (mm) for the group and reported. Skin fold thickness measurements provide an overall picture of subcutaneous fat distribution.
Outcome Time Frame
Baseline and every 4 weeks for the first 6 months after CDK 4/6 inhibitor therapy and every 3 months thereafter up to 24 months
Outcome Measure
Anthropometric measurements - Skin fold thickness (biceps, triceps, subscapular, and suprailiac)
Outcome Description
Abdominal circumference is a measurement of the horizontal distance around the abdomen. Abdominal circumference will be assessed by determining the midpoint between the lower rib margin and the iliac crest and measuring the circumference at the midpoint, in centimeters, with measuring tape while breathing normally. Group results will be summarized. An enlarged abdominal circumference can be a sign of obesity and a risk factor for disease.
Outcome Time Frame
Baseline and every 4 weeks for the first 6 months after CDK 4/6 inhibitor therapy and every 3 months thereafter up to 24 months
Outcome Measure
Anthropometric measurements - Abdominal circumference
Outcome Description
Waist-to-hip ratio will be measured with measuring tape by measuring the narrowest part of the waist followed by the widest part of the hips and dividing the waist measurement by the hip measurement. While normal values can vary, a healthy waist-to-hip ratio is generally considered to be below 0.9 for men and 0.85 for women, according to the World Health Organization (WHO). Group results will be summarized.
Outcome Time Frame
Baseline and every 4 weeks for the first 6 months after CDK 4/6 inhibitor therapy and every 3 months thereafter up to 24 months
Outcome Measure
Anthropometric measurements - Waist-to-hip ratio
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Study Population
Patients who are being asked to participate in this study because they have metastatic ER+/HER2- breast cancer, and their doctor is offering treatment with CDK 4/6 inhibitors as standard of care treatment.
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Jesus Anampa Mesias
Investigator Email
janampa@montefiore.org
Investigator Phone
718-920-4826 / 718-405-8505